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What it does 

The National Institute of Allergy and Infectious Diseases and Walter Reed Army Institute of Research convened a planning committee consisting of interdisciplinary experts to assess the ethical considerations of Zika virus human challenge trials. The committee produced a report and recommendations document that aimed to answer the following two questions:

  1. Can a Zika virus challenge trial be ethically justified; and,
  2. If so, under what conditions?

The committee examined eight major ethical considerations in the context of a potential Zika virus challenge trial:

  1. Are the risks reasonable, minimized, and justified by the potential social value of the trial?
  2. Are vulnerable populations protected?
  3. Is there a robust informed consent process?
  4. Is the level of compensation adequate but not undue?
  5. Is the right to withdraw respected?
  6. Have independent expert reviews been conducted?
  7. Is there a system of compensation for injury?
  8. Is there a plan for community engagement?

By analyzing the current state of scientific understanding about the Zika virus with respect to these eight questions, the committee concluded that a Zika virus human challenge trial could potentially be ethically justified if the Zika epidemic was quickly diminishing and field study became too difficult to conduct. The committee further explained that the social value of a human challenge trial is significant if the trial would be likely to accelerate the creation of a vaccine that could be used by stakeholders. But the committee advised that utilizing a human challenge trial to simply study the nature of the Zika virus would not be ethically justifiable because other methods for such study are available.

Yet despite these conclusions, the committee determined that at this time a Zika virus human challenge trial is not ethically justifiable because much is still unknown about the disease and its potential risk to trial participants and third parties. Should these conditions change, however, the committee suggested revisiting the ethical considerations and recommendations present in the report to determine if a specific research study proposing a Zika virus human challenge trial is ethically sound.

Recommendations for future studies included the following:

  • Only enroll individuals with the capacity to provide their voluntary and informed consent, while minimizing the risk to fetuses;
  • Use a robust informed consent process;
  • Pay volunteers fairly for their time and inconvenience, so long as those volunteers demonstrate understanding of the risks and uncertainties involved;
  • Respect participants’ right to withdraw from the study, even if they will have to remain confined to protect themselves or others;
  • Conduct an external evaluation of risk by relevant experts prior to beginning the study;
  • Ensure adequate and fair insurance coverage for research sites to cover the costs of care and compensation for research-related injury; and
  • Perform community engagement with the geographical community surrounding the study site(s) in advance of the research.
Relevant Science 

Zika virus is an emerging disease caused by a Flavivirus. It often does not present symptoms in those who are affected. If infected persons do become symptomatic, they most often experience fever, rash, headache, joint pain, pinkeye, and/or muscle pain. According to the CDC, there have been over 41,000 symptomatic cases reported in the United States since 2015.

 Zika virus is predominantly transmitted through the bite of the Aedes egypti mosquito, which inhabits much of the southern United States, as well as tropical and subtropical areas in Central America, the Caribbean, South America, Africa, the Pacific Islands, and Asia. The virus can also be spread through vaginal, anal, and oral sexual activity, through blood transfusions, and from mother to fetus during pregnancy. Infected persons can infect others even when they are not symptomatic, and it is unknown how long Zika virus can survive in a host.

The CDC notes that mother to fetus transmission is particularly concerning as Zika virus has been shown to cause microcephaly in fetuses. This condition stunts brain development and results in birth defects, such as a smaller than average head and related health problems. Zika virus has also been associated with Guillan-Barré Syndrome, a disease in which the immune system attacks the nerve cells.

Much is still unknown regarding the nature of Zika virus and its potential long-term effects. There is currently no approved medication or vaccine available for Zika treatment or prevention. The CDC’s current prevention recommendations include avoiding mosquito bites, avoiding travel in areas where Zika virus is prevalent, and using condoms. Women are strongly cautioned to refrain from becoming pregnant for at least eight weeks after exposure.

One method of researching potential vaccinations for viruses, such as Zika, is the human challenge trial, also known as a controlled human infection model. A human challenge trial is a research trial in which volunteers are knowingly infected with a pathogen—in this case Zika virus—in a controlled manner. The method is often utilized to evaluate potential medications or vaccines for a given disease. The greatest benefit of the human challenge trial is that it can expedite the vaccination or medication development process by demonstrating safety and effectiveness more quickly than other methods. However, a single research study would likely not result in the approval of a treatment or prophylactic. Additionally, a human challenge trial could also help researchers further understand Zika virus transmission.

Why It Matters 

The report and recommendations presented by this committee create a comprehensive review of ethical considerations for Zika virus human challenge trials to be used by current and future researchers. In doing so, the committee also developed ethical recommendations which can be more broadly applied to clinical research of other dangerous diseases that have no known treatment or medical prophylactic.

This report was particularly pertinent at the time of its publishing as a major epidemic of Zika virus had started in 2015, in which Zika spread from Brazil to other parts of South America and North America. The lack of existing preventative medicine and medical treatment for the disease spurred a large scientific response to developing a vaccine.

Endorsements & Opposition 

Endorsement:

  • Dr. Anthony Fauci, director of the National Institute for Allergy and Infectious Disease, stated in an interview: “The bottom line of the ethics review is right now the way protocols are written and the way people are talking about it, it isn’t ethically sound to do it. But these obstacles can be overcome.” Fauci agreed with the current outcome of the committee’s report.

Opposition:

  • Dr. Anna P. Durbin, Professor at Johns Hopkins University Vaccine Initiative, stated in an interview: “I am not sure the committee had adequate information in making their recommendation. I think they overstepped. There is a pathway forward in the recommendations, but unfortunately it is a very narrow pathway, and it does limit the value of the controlled human infection model.” Durbin believes that specific questions about Zika virus could only be answered by utilizing a human challenge trial. She also noted that the Zika virus epidemic may begin waning soon, which would make other methods of human trials difficult to conduct.  
Status 

The report was issued in February 2017. Although it was commissioned by government agencies, the report is not a regulatory document; therefore, government agencies have no mandate to follow its recommendations.

Organizations 

The National Institute of Allergy and Infectious Diseases and Walter Reed Army Institute of Research were responsible for convening the committee that authored the report. The individual authors’ names and affiliations can be found on page two of the report; most authors are university professors or medical doctors.

Primary Author 
Hayley Farless
Editor(s) 
Nicole Kastelic; Andrew Pericak, MEM
Recommended Citation 

Duke SciPol, “Ethical Considerations for Zika Virus Human Challenge Trials (Report)” available at http://scipol.duke.edu/content/ethical-considerations-zika-virus-human-challenge-trials-report (06/19/2017).

License 
Creative Commons License This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License. Please distribute widely but give credit to Duke SciPol and the primary author(s) listed above, linking back to this page if possible.